title: Inhibition of acid sensing ion channel currents by lidocaine in cultured mouse cortical neurons.
abstract: BACKGROUND
  Lidocaine is a local anesthetic that has multiple pharmacological effects including antiarrhythmia, antinociception, and neuroprotection. Acid sensing ion channels (ASICs) are proton-gated cation channels that belong to the epithelial sodium channel/degenerin superfamily. Activation of ASICs by protons results in sodium and calcium influx. ASICs have been implicated in various physiological processes including learning/memory, nociception, and in acidosis-mediated neuron injury. In this study, we examined the effect of lidocaine on ASICs in cultured mouse cortical neurons.
  
  
  METHODS
  ASIC currents were activated and recorded using a whole-cell patch-clamp technique in cultured mouse cortical neurons. The effects of lidocaine at different concentrations were examined. To determine whether the inhibition of lidocaine on ASIC currents is subunit specific, we examined the effect of lidocaine on homomeric ASIC1a and ASIC2a currents expressed in Chinese hamster ovary cells.
  
  
  RESULTS
  Lidocaine significantly inhibits the ASIC currents in mouse cortical neurons. The inhibition was reversible and dose dependent. A detectable effect was noticed at a concentration of 0.3 mM lidocaine. At 30 mM, ASIC current was inhibited by approximately 90%. Analysis of the complete dose-response relationship yielded a half-maximal inhibitory concentration of 11.79 ± 1.74 mM and a Hill coefficient of 2.7 ± 0.5 (n = 10). The effect is rapid and does not depend on pH. In Chinese hamster ovary cells expressing different ASIC subunits, lidocaine inhibits the ASIC1a current without affecting the ASIC2a current.
  
  
  CONCLUSIONS
  ASIC currents are significantly inhibited by lidocaine. Our finding reveals a new pharmacological effect of lidocaine in neurons.
authors.affiliation: Department of Anesthesiology, SUNY Downstate Medical Center, 450 Clarkson Ave., Box 6, Brooklyn, NY 11203, USA. jun.lin@downstate.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Xiangping
authors.initials: X
authors.lastname: Chu
authors.forename: Samaneh
authors.initials: S
authors.lastname: Maysami
authors.forename: Minghua
authors.initials: M
authors.lastname: Li
authors.forename: Hongfang
authors.initials: H
authors.lastname: Si
authors.forename: James E
authors.initials: JE
authors.lastname: Cottrell
authors.forename: Roger P
authors.initials: RP
authors.lastname: Simon
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xiong
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D008012:Lidocaine / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D008012:Lidocaine